Neoplasia screening compositions and methods of use

Abstract

As described in more detail below, the present invention generally features compositions and non-invasive methods useful for the screening, identification, monitoring, or diagnosis of subjects having a neoplasia. The invention further provides highly accurate non-invasive methods for the staging or selection of treatment for a bladder, renal, or prostate cancer in a subject.

Description

CROSS-REFERENCE TO RELATED APPLICATION[0001]This application claims the benefit of the following U.S. Provisional Application Nos. 60 / 652,594, which was filed on Feb. 14, 2005; 60 / 653,295, which was filed on Feb. 16, 2005; 60 / 652,591, which was filed on Feb. 14, 2005; and 60 / 652,590, which was filed on Feb. 14, 2005; each of which is hereby incorporated by reference in their entirety.BACKGROUND OF THE INVENTION[0002]Neoplasias, including bladder, renal, and prostate cancers, are a significant cause of human morbidity and mortality. Bladder cancer is the fourth most common cancer in men and the eighth in women both in terms of incidence and mortality; renal cancer kills approximately 12,000 Americans every year, and 30,000 new cases of renal cancer are reported each year in the United States; and prostate cancer is clinically diagnosed in one of every 11 American men. One third of men diagnosed will prostate cancer will develop a life threatening disease In their earliest stages, bla...

AI Technical Summary

Benefits of technology

[0056]In various embodiments of any of the above aspects, the promoter is any one or more (e.g., two, three, four, five, six, seven, eight, nine, ten, or eleven) of p16, ARF, GSTP1, MGMT, RAR-β2, TIMP3, CDH1, RASSF1A, APC, LOXL1, or LOXL4 and the promoter methylation is determined at two, three, or four, five, six, seven, eight, or nine promoters. In other embodiments of any of the above aspects, the promoter methylation is determined for a group of promoters including p16, ARF, GSTP1, MGMT, RAR-β2, TIMP3, CDH1, RASSF1A, LOXL1, LOXL4, and / or APC. In yet other embodiments of the above aspects, the promoter methylation at a selected promoter (e.g., a promoter is selected from any one or more of p16, ARF, GSTP1, MGMT, RAR-β2, TIMP3, CDH1, RASSF1A, LOXL1, LOXL4, and APC) is compared to a reference (e.g., the level of methylation present in a sample previously obtained from the subject; a baseline level of methylation present in a sample from the subject obtained prior to therapy; or the level of methylation present in a normal subject sample. In still other embodiments of the above aspects, the level of methylation at a promoter (e.g., ARF and MGMT methylation) is indicative of tumor stage, correlate with increasing tumor (T) stage. In still other embodiments, an altered level of promoter methylation is an increase or decrease in promoter methylation. In still other embodiments, the increase in promoter methylation indicates that more aggressive therapy is appropriate. In still other embodiments, the altered level is an increase or a decrease in the level of promoter methylation relative to a reference. In various embodiments of the above aspects, the increase in p16, ARF, MGMT, and GSTP1 promoters is determined. In still other embodiments, the level of promoter methylation at an increased number of promoters increases specificity or increases sensitivity. In still other embodiments of any of the above aspects, the biological sample is a tissue sample, a biological sample that contains genetic material, such as any one or more of serum, plasma, ejaculate, urine or stool.

Problems solved by technology

Neoplasias, including bladder, renal, and prostate cancers, are a significant cause of human morbidity and mortality.

When and if clinical symptoms do develop, patient diagnosis typically involves invasive procedures that lack sensitivity and accuracy.

Images